Introduction Trophoblast dysfunction and abnormal cell death are associated with unexplained spontaneous miscarriage (USM), while the underlying mechanisms remain unclear. This research aims to elucidate the pathogenic functions of the RNA-binding protein KH-type splicing regulatory protein (KHSRP) in USM. Methods We first identified reduced KHSRP expression in USM villi by performing integrative analysis of our and public RNA-seq data, followed by validation in clinical samples via RT-qPCR, western blotting, and immunohistochemistry. Functional studies in HTR-8/SVneo and JEG-3 cells with siRNA knockdown and plasmid overexpression assessed proliferation, apoptosis, cell-cycle progression, and DNA damage through CCK-8, EdU, flow cytometry, and immunofluorescence. Downstream targets of KHSRP were identified by integrating siKHSRP RNA-seq, villi RNA-seq, and RIP-seq data, and subsequently validated at both the transcript and protein levels. In vivo, placental Khsrp knockdown was achieved via intrauterine injection of self-complementary adeno-associated virus8 carrying a short hairpin RNA (shRNA) targeting the Khsrp gene (scAAV-shKhsrp). Results KHSRP was downregulated in USM villi. In trophoblast cells, KHSRP loss impaired proliferation, caused G2/M arrest, and triggered DNA damage accumulation and apoptosis in a p53-independent manner. Mechanistically, KHSRP bound and destabilized tissue factor pathway inhibitors 2 (TFPI2) mRNA. KHSRP deficiency upregulated TFPI2, promoting DNA damage accumulation and apoptosis. In mice, intrauterine scAAV-shKhsrp injection induced embryo resorption, placental structural abnormalities, and increased TFPI2 expression. Discussion KHSRP is downregulated in USM villi, and its loss elevates TFPI2 by impairing mRNA decay, leading to DNA-damage accumulation and trophoblast apoptosis. Thus, KHSRP and TFPI2 may serve as potential therapeutic targets for USM.
Human uterine spiral artery remodeling (SAR) is a tightly regulated process involving complex interactions between interstitial and endovascular extravillous trophoblasts (iEVTs and enEVTs) and diverse maternal decidual cell populations. However, the intrinsic spatiotemporal dynamics of SAR in human placentation remain poorly understood, largely due to the limited availability of high-quality maternal-fetal interface specimens. Electively terminated early pregnancies offer a valuable resource for studying SAR in situ, yet inconsistent methods for distinguishing fragmented villous and decidual tissues have hindered reproducibility and interpretation. Herein we present a standardized protocol for the classification and characterization of high-quality maternal-fetal interface specimens from elective terminations by integrating stereomicroscopic evaluation with confirmation by immunohistochemistry and immunofluorescence microscopy. Combined with multiplex immunofluorescence imaging with cell-type-specific markers, this approach enabled precise spatial mapping and quantification of key morphological and cellular events in SAR from gestational weeks 5–10. Our analyses reveal that SAR initiates as early as week 5 with extraluminal recruitment of natural killer (NK) cells, followed by the formation of tightly packed EVT plugs within the lumens of spiral arteries in the decidua compacta; these plugs progressively extend deeper into the vessels and gradually loosen as gestation progresses. Notably, enEVTs appear to acquire NK cell-like phenotypes that may facilitate the displacement of endothelial and smooth muscle cells, promoting progressive vessel dilation. In summary, we provide a robust and reproducible method for assessing physiological SAR in early human pregnancy, promoting the adoption of our methodology in future studies of pathological SAR and related pregnancy disorders.
To assess the overall safety and effectiveness of the etonogestrel implant radiopaque in real-world clinical settings in China. A multicenter, prospective, single-arm, observational study was conducted in women (aged ≥ 18 years) across 31 centers in China (March 2016–July 2021). The implant was prescribed as part of routine clinical practice. Primary outcomes included overall safety and topical (local) safety profile; secondary outcomes included participant and physician satisfaction and contraceptive effectiveness of the etonogestrel implant. Of 1,901 women using the etonogestrel implant, 45.4
Rare earth elements (REEs) exposure during pregnancy may increase the risk of unexplained spontaneous abortion. However, the association between REEs intrauterine exposure and unexplained spontaneous abortion had yet to be studied. In order to conduct this large case-control study, we thus collected chorionic villus from 641 unexplained spontaneous abortion and 299 control pregnant women and detected the concentrations of 15 REEs by inductively coupled plasma mass spectrometer (ICP-MS). Because the detection rates of 10 REEs were less than 80%, the remaining 5 REEs, which were lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd) and yttrium (Y), underwent to further analysis. The association between 5 REEs and unexplained spontaneous abortion was assessed by using the logistic regression, bayesian kernel regression (BKMR) and weighted quantile sum regression (WQS) models. In the adjusted logistic regression model, Pr, Nd and Y enhanced the incidence of unexplained spontaneous abortion in a dose-dependent way and Ce increased the risk only at high concentration group. The result of BKMR demonstrated that the risk of unexplained spontaneous abortion increased as the percentile of five mixed REEs increased. Y and Nd were both significantly associated with an increased incidence of unexplained spontaneous abortion, but La was correlated with a decrease in the risk of unexplained spontaneous abortion. Pr was substantially associated with an increase in the risk of unexplained spontaneous abortion when other REEs concentrations were fixed at the 25th and 50th percentiles. According to WQS regression analysis, the WQS index was significantly associated with unexplained spontaneous abortion (OR=3.75, 95% CI:2.40-5.86). Y had the highest weight, followed by Nd and Pr, which was consistent with the analysis results of our other two models. In short, intrauterine exposure to REEs was associated with an increased risk of unexplained spontaneous abortion, with Y, Nd and Pr perhaps playing an essential role.
Decidual natural killer (dNK) cells are the most abundant immune cells at the maternal-fetal interface during early pregnancy in both mice and humans, and emerging single-cell transcriptomic studies have uncovered various human dNK subsets that are disrupted in patients experiencing recurrent early pregnancy loss (RPL) at early gestational stage, suggesting a connection between abnormal proportions or characteristics of dNK subsets and RPL pathogenesis. However, the functional mechanisms underlying this association remain unclear. Here, we established a mouse model by adoptively transferring human dNK cells into pregnant NOG (NOD/Shi-scid/IL-2Rγnull) mice, where human dNK cells predominantly homed into the uteri of recipients. Using this model, we observed a strong correlation between the properties of human dNK cells and pregnancy outcome. The transfer of dNK cells from RPL patients (dNK-RPL) remarkably worsened early pregnancy loss and impaired placental trophoblast cell differentiation in the recipients. These adverse effects were effectively reversed by transferring CD56+CD39+ dNK cells. Mechanistic studies revealed that CD56+CD39+ dNK subset facilitates early differentiation of mouse trophoblast stem cells (mTSCs) towards both invasive and syncytial pathways through secreting macrophage colony-stimulating factor (M-CSF). Administration of recombinant M-CSF to NOG mice transferred with dNK-RPL efficiently rescued the exacerbated pregnancy outcomes and fetal/placental development. Collectively, this study established a novel humanized mouse model featuring functional human dNK cells homing into the uteri of recipients and uncovered the pivotal role of M-CSF in fetal-supporting function of CD56+CD39+ dNK cells during early pregnancy, highlighting that M-CSF may be a previously unappreciated therapeutic target for intervening RPL.
Objective: To investigate whether operative hysteroscopy in addition to vacuum aspiration for the management of early pregnancy loss effectively increases the success rate of subsequent frozen embryo transfer. Design: Propensity score-matched cohort study. Setting: Academic hospital. Patient(s): Women with a miscarriage at 5-16 gestational weeks during an in vitro fertilization cycle in Peking University Third Hospital from 2015 to 2022. Intervention(s): Hysteroscopy plus vacuum aspiration vs. conventional vacuum aspiration. Main Outcome Measure(s): Live birth rate in the subsequent frozen embryo transfer. Result(s): A total of 347 women who underwent vacuum aspiration plus hysteroscopy and 2,562 women who underwent conventional vacuum aspiration were included in the analysis. After propensity score matching (1:1 ratio), 325 women were included in each group. Compared with women who underwent vacuum aspiration, those who underwent vacuum aspiration plus hysteroscopy were associated with a lower rate of live birth in the propensity score-based matched cohort (22% vs. 30%; adjusted odds ratio, 0.68 [0.47-0.97]). Biochemical, clinical, and multiple pregnancy rates were not significantly different, as was the miscarriage rate. In the overall cohort, 11 women experienced surgery reintervention in the vacuum aspiration group (0.4%), whereas none required surgery reintervention in the vacuum aspiration plus hysteroscopy group. Conclusion(s): Women who underwent vacuum aspiration plus hysteroscopy may be associated with lower rates of live birth than those who underwent vacuum aspiration. Further studies are necessary to establish this relationship definitively. (Fertil Steril (R) 2024;122:1134-43. (c) 2024 by American Society for Reproductive Medicine.)
PSD502 is a metered-dose spray for premature ejaculation. The two trials aimed to evaluate the safety and pharmacokinetics of PSD502 in healthy Chinese male and female individuals. Two phase I, randomized, double-blind, placebo-controlled trials were conducted in men (Trial 1) and women (Trial 2). The participants were randomized 3:1 to receive PSD502 (7.5 mg of lidocaine and 2.5 mg of prilocaine per spray) or a placebo. For male individuals, a single dose (three sprays) once daily was applied to the glans penis for 21 days except for nine sprays (three doses) on days 7 and 14, 4 h apart for each dose. For female individuals, two sprays were applied to the vagina and one to the cervix once daily for 7 days. The primary endpoint was safety. Pharmacokinetics analysis was also performed. Twenty-four male and 24 female individuals were recruited. Treatment-emergent adverse events occurred in 38.9
异常子宫出血( abnormal uterine bleeding,AUB)是指源于子宫腔的,与正常月经的周期规律、经期长度及出血量等任何一项不符的异常出血[1] ,是一种常见的普通妇科疾病,影响10% ~30%女性患者的健康及生活质量[2].关于育龄期非妊娠妇女AUB 的病因,目前统一采用国际妇产科联盟( FIGO )推荐的 PALM-COEIN 系统[3] ,其中约 50%为排卵障碍所致的异常子宫出血(AUB-ovulatory dysfunction,AUB-O),是 AUB 最常见的病因[4] ,有手术及非手术治疗方法可供患者选择,大多数可通过药物治疗取得良好的效果.对于有雌激素禁忌证的女性来说,孕激素制剂是治疗 AUB 的理想选择.在育龄期或围绝经期妇女中,孕激素可用于调节月经间期出血、月经量过多;在更年期妇女中,孕激素可用于预防子宫内膜增生,减少子宫内膜癌的发生.同时,孕激素亦可与其它激素相互作用,影响乳腺、心血管系统及骨骼系统等.
目的 探讨包块型剖宫产瘢痕妊娠(cesarean scar pregnancy,CSP)的临床特点及治疗方法.方法 回顾性分析2010年1月~2020年12月我院28例包块型CSP的临床特征及诊治情况.均有人流、药流或清宫史,术后异常阴道出血21例(其中失血性休克3例),血hCG下降不理想7例.入院距上次手术时间1~120 d,中位数21 d,其中<2周6例.包块直径14~66(35.3±14.7)mm;包块与膀胱间子宫肌层厚度1~5(1.7±1.0)mm.血β-hCG>1000 mIU/ml 18例(64.3%).行宫腔镜手术10例,宫、腹腔镜联合手术9例,腹腔镜手术5例,开腹手术4例.结果 行CSP残留组织清除27例,其中13例同时行剖宫产瘢痕修补,联合双侧子宫动脉栓塞或双侧子宫动脉上行支阻断6例,联合甲氨蝶呤治疗4例;腹腔镜全子宫双侧输卵管切除1例.手术均顺利完成,无并发症发生.其中5例术中或术后输悬浮红细胞400 ml.术后18~52 d(中位数26 d)血β-hCG降至正常范围.除全子宫切除术患者,余27例术后21~54 d月经复潮.结论 剖宫产瘢痕处剩余肌层薄和包块大是包块型CSP的两个重要特点,可采用联合治疗以减少并发症,提高疗效.
Stress urinary incontinence (SUI) is a common postpartum disorder. In this study, we aim to identify the risk factors for SUI in multiparous women 1 year after delivery. A retrospective cohort study was conducted in multiparous women who gave birth from January 2016 to March 2018 in Peking University Third Hospital. We interviewed all of the participants with the help of The International Consultation on Incontinence questionnaire short form (ICI-Q-SF) 1 year after delivery by telephone to identify symptoms of SUI. Univariate and multivariate analyses were applied to assess the potential risk factors of SUI. A decision tree was used to assess the prevalence of SUI in the different subgroups. A total of 172 multiparous women were recruited. The prevalence of SUI was 30.2% (52/172) 1 year after delivery. In univariate analysis, maternal age ≥ 35 years, SUI after the first delivery, GDM and birth exclusively by vaginal delivery increased the risk for SUI 1 year after delivery. Multivariate analysis indicated that SUI after the first delivery (OR: 3.937, 95% CI: 1.764–8.787), gestational diabetes mellitus (GDM) (OR: 3.754, 95% CI: 1.599–8.810) and age ≥ 35 years (OR: 2.964, 95% CI: 1.208–7.274) were independent risk factors for SUI 1 year after delivery. A decision tree showed that participants who had SUI after the first delivery and patients with GDM were more likely to have SUI than patients without GDM (73.3% vs. 50%). For multiparous women, SUI after the first delivery, GDM and age ≥ 35 years increase the risk of SUI 1 year after delivery.
目的:分析子宫动静脉畸形(arteriovenous malformations,AVMs)的病因及临床表现,探讨诊治中的注意事项.方法:回顾分析北京大学第三医院(我院)2014年3月—2018年3月收治的5例子宫AVMs的临床资料,并结合文献讨论.结果:5例经阴道彩色多普勒超声检查初步诊断为子宫AVMs,1例宫腔镜下清宫+宫腔球囊压迫,3个月后复查病变消失;1例超声引导下清宫,3个月后复查病变消失;另外3例经血管造影确诊,同时行选择性子宫动脉栓塞,1例术后2+年成功分娩,1例术后2个月闭经,1例栓塞后清宫,术后3个月复查病变消失.结论:经阴道彩色多普勒超声可作为子宫动静脉畸形的首选检查方法,血管造影是诊断的金标准.选择性子宫动脉栓塞是控制子宫出血的有效方法.
Abstract. Background. Preeclampsia (PE) is a serious complication that affects maternal and perinatal outcomes. However, the mechanisms have not been fully explained. This study was designed to analyze longitudinal gut microbiota alterations in pregnant women with and without PE in the second (T2) and third trimesters (T3). Methods. In this nested case-control study, which was conducted at Nanjing Maternity and Child Health Care Hospital, fecal samples from 25 PE patients (25 fecal samples obtained in T2 and 15 fecal samples obtained in T3) and 25 matched healthy controls (25 fecal samples obtained in T2 and 22 fecal samples obtained in T3) were collected, and the microbiota were analyzed using 16S rRNA gene sequencing. The diversity and composition of the microbiota of PE cases and controls were compared. Results. No significant differences in diversity were found between the PE and control groups (P > 0.05). In the control group, from T2 to T3, the relative abundances of Proteobacteria (median [Q1, Q3]: 2.25% [1.24%, 3.30%] vs. 0.64% [0.20%, 1.20%], Z = −3.880, P < 0.05), and Tenericutes (median [Q1, Q3]: 0.12% [0.03%, 3.10%] vs. 0.03% [0.02%, 0.17%], Z = −2.369, P < 0.05) decreased significantly. In the PE group, the relative abundance of Bacteroidetes in T2 was lower than in T3 (median [Q1, Q3]: 18.16% [12.99%, 30.46%] vs. 31.09% [19.89%, 46.06%], Z = −2.417, P < 0.05). In T2, the relative abundances of mircrobiota showed no significant differences between the PE group and the control group. However, in T3, the relative abundance of Firmicutes was significantly lower in the PE group than in the control group (mean ± standard deviation: 60.62% ± 15.17% vs. 75.57% ± 11.53%, t = −3.405, P < 0.05). The relative abundances of Bacteroidetes, Proteobacteria, and Enterobacteriaceae were significantly higher in the PE group than in the control group (median [Q1, Q3]: 31.09% [19.89%, 46.06%] vs. 18.24% [12.90%, 32.04%], Z = −2.537, P < 0.05; 1.52% [1.05%, 2.61%] vs. 0.64% [0.20%, 1.20%], Z = −3.310, P < 0.05; 0.75% [0.20%, 1.00%] vs. 0.01% [0.004%, 0.023%], Z = −4.152, P < 0.05). Linear discriminant analysis combined effect size measurements analysis showed that the relative abundances of the phylum Bacteroidetes, class Bacteroidia and order Bacteroidales were increased in the PE group, while those of the phylum Firmicutes, the class Clostridia, the order Clostridiales, and the genus unidentified Lachnospiraceae were decreased in the PE group; and these differences were identified as taxonomic biomarkers of PE in T3. Conclusion. From T2 to T3, there was an obvious alteration in the gut microbiota. The gut microbiota of PE patients in T3 was significantly different from that of the control group.
目的 探讨不同中期引产方案的有效性及安全性.方法 对北京大学第三医院2015年1月至2017年12月收治的237例由于病理因素进行中期引产的病例进行回顾性分析,采用logistic回归方法对不同引产方案在中期引产中的临床特征进行单因素和多因素分析.结果 中期引产采用单一方案161例,联合方案76例.单因素回归分析结果提示,与单一方案相比,联合方案的孕次、产次和剖宫产史(36.84% vs.14.28%)比例更高(均P<0.05),胎盘异常(11.84% vs.3.73%,P<0.05)和高血压疾病(23.68% vs.13.04%,P<0.05)的比例也显著升高,多胎妊娠的比例下降(2.63% vs.11.18%,P<0.05),联合引产方案的平均孕周为(23.40±3.46)周,与单一方案(21.20±4.08)周相比差异具有统计学意义(P<0.05).多因素回归分析结果提示,剖宫产史、孕周和孕次是决定妊娠中期选择联合引产方案的影响因素(P< 0.05).结论 当中期引产患者存在既往多次妊娠史、剖宫产史以及孕周接近24周等高危因素时,需要考虑采用联合方案以降低引产失败的可能性,达到有效减少并发症,保障患者安全的目的.
Proper development of fetal germ cells (FGCs) is vital for the precise transmission of genetic and epigenetic information through generations. The transcriptional landscapes of human FGC development have been revealed; however, the epigenetic reprogramming process of FGCs remains elusive. Here, we profiled the genome-wide DNA methylation and chromatin accessibility of human FGCs at different phases as well as gonadal niche cells at single-cell resolution. First, we found that DNA methylation levels of FGCs changed in a temporal manner, whereas FGCs at different phases in the same embryo exhibited comparable DNA methylation levels and patterns. Second, we revealed the phase-specific chromatin accessibility signatures at the promoter regions of a large set of critical transcription factors and signaling pathway genes. We also identified potential distal regulatory elements including enhancers in FGCs. Third, compared with other hominid-specific retrotransposons, SVA_D might have a broad spectrum of binding capacity for transcription factors, including SOX15 and SOX17. Finally, using an in vitro culture system of human FGCs, we showed that the BMP signaling pathway promoted the cell proliferation of FGCs, and regulated the WNT signaling pathway by orchestrating the chromatin accessibility of its ligand genes. Our single-cell epigenomic atlas and functional assays provide valuable insights for understanding the strongly heterogeneous, unsynchronized, yet highly robust nature of human germ cell development.
The developmental pathway of the neural retina (NR) and retinal pigment epithelium (RPE) has been revealed by extensive research in mice. However, the molecular mechanisms underlying the development of the human NR and RPE, as well as the interactions between these two tissues, have not been well defined. Here, we analyzed 2,421 individual cells from human fetal NR and RPE using single-cell RNA sequencing (RNA-seq) technique and revealed the tightly regulated spatiotemporal gene expression network of human retinal cells. We identified major cell classes of human fetal retina and potential crucial transcription factors for each cell class. We dissected the dynamic expression patterns of visual cycle- and ligand-receptor interaction-related genes in the RPE and NR. Moreover, we provided a map of disease-related genes for human fetal retinal cells and highlighted the importance of retinal progenitor cells as potential targets of inherited retinal diseases. Our findings captured the key in vivo features of the development of the human NR and RPE and offered insightful clues for further functional studies.
动静脉畸形( arteriovenous malformations,AVMs)是由于血管连接异常引起大量的或者不规则出血而危及生命,可发生在全身各脏器.而子宫 AVMs 是指子宫的动脉与静脉之间形成的异常交通,可导致反复顽固的阴道出血,严重时可危及生命.子宫 AVMs 比较罕见,患病率目前未知,国外文献中目前只有约 100 例的报道[1] .由于多普勒超声、计算机断层扫描( computed tomography, CT )及核磁共振成像( magnetic resonance imaging,MRI)等影像学手段的日益普及,报告的病例呈上升趋势.宫腔操作一般用于处理异常出血,可能会导致大出血,因此在操作之前,准确的临床和影像学诊断是非常必要的.
目的 分析经产妇产后早期(6~8周)压力性尿失禁(Stress urinary incontinence,SUI)的临床危险因素.方法 回顾性分析于北京大学第三医院2016年1月至2017年10月分娩及产后复查的141例经产妇临床资料,依据尿失禁简表(ICIQ-UI)确诊SUI 81例,非SUI即对照组60例,比较两组的相关危险因素.结果单因素分析显示,与非SUI组相比,经产妇产后早期SUI组的前次阴道分娩和末次阴道分娩比例明显升高(63.2%vs 36.8%,P=0.016;63.3%vs36.7%,P=0.009).前次阴道分娩合并会阴侧切和会阴裂伤经产妇发生产后早期SUI比例升高(66.1%vs33.9%,P=0.014;76.2%vs23.8%,P=0.009).末次阴道分娩无会阴侧切或裂伤、合并会阴侧切、合并会阴裂伤三种情况的经产妇产后早期SUI是末次剖宫产分娩的1.6倍、2.0倍以及1.7倍(RR:1.594,P=0.095;RR:1.939,P=0.043;RR:1.723,P=0.014).末次妊娠时年龄、孕前体质指数、孕期体重增加、新生儿体重、妊娠期糖尿病等因素,在两组之间差异均无统计学意义(P>0.05).多因素分析显示,末次阴道分娩是经产妇产后早期SUI的独立危险因素(OR=2.939 95% CI:1.232~7.009,P=0.015).结论 末次分娩方式为阴道分娩的经产妇发生产后早期SUI风险明显增加,并及时给予指导和必要的干预.
Objective To investigate the variants in the high frequency associated with corresponding diseases in Chinese population,and to identify disease coverage for carriers screening in China.Methods A total of 200 normal and unrelated Chinese samples who accepted whole exome sequencing in Novogene Co.Ltd from July 2017 to July 2018 were subjected to screen for the genes associated with 133 single-gene recessive diseases.Then the variants were identified and interpreted by American College of Medical Genetics and Genomics (ACMG) guidelines,which were analyzed as pathogenic or benign.A total variants detected in all of the sample were counted.Results It was found that the variants related to thyroid dyshormonogenesis,non-syndromic deafness and retinitis pigmentosa were not only highly carried in the Chinese population,but also had many mutation types.In addition,a total of 78 variants were identified.And 4 of them (MYO15A c.5919G>A,TYR c.929_930insC,DUOX2 c.3329G>A,ABCB 11 c.2842C>T) were analyzed as pathogenic mutations,which were heterozygous and carried by four individuals.Moreover,9 novel mutations were found that have never been reported,and these mutations were considered as uncertain significance.Conclusion High-frequency genetic mutations with the corresponding diseases were identified in 200 Chinese populations.Preliminary conclusions indicate that thyroid dyshormonogenesis,non-syndromie deafness and retinitis pigmentosa can be the focus for carriers screening in China.
Objective To explore the teaching outcome of medical ethics course jointly by clinical teachers and humanities teachers. Methods A total of 286 students from eight-year curriculum enrolled from 2007 to 2013 in Health Science Center Peking University were selected for clinical practice in Peking University Third Hospital from May 2012 to May 2018, Four clinical teachers and two medical humanities teachers form medical ethics teaching team, Medical ethics is taught for two months a year in total 30 hours. Every year after the end of the course, the students'acceptance of medical ethics teaching team is investigated by questionnaire, and the teaching outcome is evaluated. Results There were 86. 7% ( 248/286) students expressed their interest in medical ethics, 83. 2% (238/286) students thought that the study of the medical ethics could adjust their clinical thinking, 78% ( 223/286) students also hoped to discuss further, 93. 4%(267/286) students expressed their satisfaction with medical ethics, 54. 9%(157/286)students thought the course of medical ethics should run through the stages of basic medicine science, clinical medicine and secondary discipline stage. Conclusions The physicians' participation in the teaching of medical humanities courses stimulate students' interest, Improve students' learning satisfaction. Medical ethics learning should run through all stages of medical learning.